Modulation of IL33/ST2 axis and mucosal healing in IBD: state of the art and future perspectives

Inflammatory bowel disease (IBD), comprising Ulcerative Colitis and Crohn's disease, represent a chronic condition of the gastrointestinal tract characterized by an immunological alteration and weakening of mucosal barrier. Mucosal healing and inflammation resolution have emerged as critical therapeutic goals, strongly associated with sustained remission and improved clinical outcomes. Over the years, numerous studies have explored various therapeutic strategies, with increasing focus on biologics and small molecules. One of the emerging immunological targets in IBD is the interleukin 33 (IL-33) / suppression of tumorigenicity 2 (ST2) axis, which exhibits both proinflammatory and anti-inflammatory functions. Evidence from in-vitro and in-vivo studies highlights the involvement of IL-33/ST2 signaling in epithelial regeneration and mucosal healing, but also in pathogenesis of the disease. Several approaches to modulate this axis have been explored, including monoclonal antibodies, receptor antagonists, and small molecules. Concurrently, in-silico molecular design represents a promising strategy for identifying novel therapeutic agents. In particular, numerous computer-aided drug design (CADD) studies have focused on the IL-33/ST2 complex and its role in maintaining intestinal barrier function. This review provides a comprehensive overview of the IL-33/ST2 axis in IBD, on mucosal healing and potential modulation strategies, such as computational approaches.